Epigallocatechin gallate (EGCG) and other tea catechins have previously been used as antibacterial agents, and examples for such activity are well known in the art (see e.g., Jpn. J. Bacteriol. (1991); 46: 839-845). However, to exhibit significant antibacterial effect, dosages are generally very high and are therefore typically not achieved in physiological conditions or in vivo. Similar high concentrations were reported by Shimamura in U.S. Pat. No. 5,358,713 using selected catechins to prevent transmission of MRSA to another person.
To reduce minimum inhibitory concentration of certain antibiotic drugs, antibiotic drugs were combined with certain catechins, and selected catechins were reported to be sensitizing agents for amikacin, chloramphenicol, and various beta-lactam antibiotics as described by Shimamura in U.S. Pat. No. 5,807,564. Similarly, rose polyphenols were reported to reduce the minimum inhibitory concentration of various beta-lactam antibiotics (see e.g., Microbiol Immunol. 2004; 48(1):67-73.). However, and at least for some of the catechins, the effective concentrations require were still relatively high. In other attempts to treat MRSA infections, selected catechins were also combined with specific theaflavin compounds as described in EP 0 761 226 to produce an antimicrobial composition. Unfortunately, the same difficulties remained with respect to certain catechins. In yet further known combinations of selected catechins, Morree et al disclosed in U.S. Pat. No. 6,652,890 a mixture of EGC and EC that was effective in inhibiting NADH oxidase of neoplastic cells that express NOX to thereby treat cancer. However, the effect of such combination on bacteria was not reported in that reference.
In still further known attempts to use catechins as antibiotic drugs, various catechins were chemically modified as described by Stapleton et al in WO 2005/034976. While such modified catechins provided remarkable antibacterial effect as compared to their unmodified counterparts, synthesis and purification increases cost, and administration to human has not yet been proven safe and effective.
Thus, while numerous compositions and methods for eradicating and/or sensitizing MRSA to various antibiotics are known in the art, all or almost all of them suffer from one or more disadvantages. Therefore, there is still a need for improved pharmaceutical agents for treatment and/or chemoprevention of infections with MRSA.